Karim Hamaoui1, Sally Gowers2, Samir Damji3, Michelle Rogers2, Chi Leng Leong2, George Hanna3, Ara Darzi3, Martyn Boutelle2, Vassilios Papalois4. 1. Department of Surgery, Imperial College London, London, United Kingdom. Electronic address: karim.hamaoui08@imperial.ac.uk. 2. Department of Bioengineering, Imperial College London, London, United Kingdom. 3. Department of Surgery, Imperial College London, London, United Kingdom. 4. Department of Surgery, Imperial College London, London, United Kingdom; Imperial College Renal and Transplant Centre, Hammersmith Hospital, Imperial College Healthcare NHS Trust, London, United Kingdom.
Abstract
BACKGROUND: Viability assessment during preservation is imperative to avoid unnecessary discard of marginal organs maximizing graft outcomes in kidney transplantation. To address this need, we have developed a novel system based on a rapid sampling microdialysis (rsMD) analyzer allowing continuous tissue monitoring and measurement of metabolic markers of cell damage. Our aim was to develop a tool that allows for accurate assessment of tissue metabolism and organ viability in the preservation period. METHODS: Twenty-two porcine kidneys subjected to 15 min of warm ischemia underwent either 24 h of static cold storage (SCS) or 10 h of hypothermic machine perfusion (HMP). After preservation, tissue temperature was allowed to passively increase to ambient temperature as an ischemic challenge. Cortical and medullary metabolism was monitored throughout with online measurements of lactate concentrations made every 60 s. RESULTS: On commencement of monitoring, lactate concentrations were successfully detected within 15 mins. During the initial 1.5 h, lactate concentrations were similar during SCS (65 μM) and HMP (124 μM, P > 0.05) but lower after 10 h of SCS (SCS: 68 μM versus HMP: 230 μM, P < 0.001). Warming data suggest a resilience of HMP kidneys to subsequent temperature induced ischemia compared to SCS kidneys. CONCLUSIONS: This preliminary study provides the baseline ischemic profile for porcine kidneys while validating the technique of rsMD as a tool for organ viability assessment during preservation. The data characterize metabolic differences between SCS and HMP preserved allografts and can help elucidate why HMP is clinically superior to SCS allowing development of interventions to augment these benefits.
BACKGROUND: Viability assessment during preservation is imperative to avoid unnecessary discard of marginal organs maximizing graft outcomes in kidney transplantation. To address this need, we have developed a novel system based on a rapid sampling microdialysis (rsMD) analyzer allowing continuous tissue monitoring and measurement of metabolic markers of cell damage. Our aim was to develop a tool that allows for accurate assessment of tissue metabolism and organ viability in the preservation period. METHODS: Twenty-two porcine kidneys subjected to 15 min of warm ischemia underwent either 24 h of static cold storage (SCS) or 10 h of hypothermic machine perfusion (HMP). After preservation, tissue temperature was allowed to passively increase to ambient temperature as an ischemic challenge. Cortical and medullary metabolism was monitored throughout with online measurements of lactate concentrations made every 60 s. RESULTS: On commencement of monitoring, lactate concentrations were successfully detected within 15 mins. During the initial 1.5 h, lactate concentrations were similar during SCS (65 μM) and HMP (124 μM, P > 0.05) but lower after 10 h of SCS (SCS: 68 μM versus HMP: 230 μM, P < 0.001). Warming data suggest a resilience of HMP kidneys to subsequent temperature induced ischemia compared to SCS kidneys. CONCLUSIONS: This preliminary study provides the baseline ischemic profile for porcine kidneys while validating the technique of rsMD as a tool for organ viability assessment during preservation. The data characterize metabolic differences between SCS and HMP preserved allografts and can help elucidate why HMP is clinically superior to SCS allowing development of interventions to augment these benefits.
Authors: Sally A N Gowers; Michelle L Rogers; Marsilea A Booth; Chi L Leong; Isabelle C Samper; Tonghathai Phairatana; Sharon L Jewell; Clemens Pahl; Anthony J Strong; Martyn G Boutelle Journal: Lab Chip Date: 2019-07-10 Impact factor: 6.799
Authors: Isabelle C Samper; Sally A N Gowers; Michelle L Rogers; De-Shaine R K Murray; Sharon L Jewell; Clemens Pahl; Anthony J Strong; Martyn G Boutelle Journal: Lab Chip Date: 2019-05-16 Impact factor: 7.517
Authors: S A N Gowers; K Hamaoui; P Cunnea; S Anastasova; V F Curto; P Vadgama; G-Z Yang; V Papalois; E M Drakakis; C Fotopoulou; S G Weber; M G Boutelle Journal: Analyst Date: 2018-01-29 Impact factor: 4.616
Authors: Sally A N Gowers; Karim Hamaoui; Natalie Vallant; George B Hanna; Ara Darzi; Daniel Casanova; Vassilios Papalois; Martyn G Boutelle Journal: Anal Methods Date: 2018-11-05 Impact factor: 2.896